Genome-wide association study identifies a susceptibility locus for HCV-induced hepatocellular carcinoma
Genome-wide association study identifies a susceptibility locus for HCV-induced hepatocellular carcinoma
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DOI：
10.1038/ng.809
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发表时间：
2011-05-01
期刊：
影响因子：
30.8
通讯作者：
Matsuda, Koichi
中科院分区：
文献类型：
--
作者：
Kumar, Vinod;Kato, Naoya;Matsuda, Koichi
为了确定丙型肝炎病毒诱发的肝细胞癌（HCV 诱发的 HCC）的遗传易感因素，我们利用 721 名 HCV 诱发的 HCC 个体（病例）和 2,890 名日本裔 HCV 阴性对照患者的 432,703 个常染色体 SNP 进行了全基因组关联研究。在全基因组关联研究中显示出可能关联的 8 个 SNP（P < 1 x 10(-5)）在 673 例病例和 2,596 名对照中进一步进行了基因分型。我们在 6p21.33 上的 MICA 5' 侧翼区域发现了一个先前未识别的位点（rs2596542，P-combined = 4.21 x 10(-13)，比值比 = 1.39）与 HCV 诱导的 HCC 密切相关。随后对慢性丙型肝炎 (CHC) 患者进行的分析表明，该 SNP 与 CHC 易感性无关 (P = 0.61)，但与从 CHC 进展为 HCC 显着相关 (P = 3.13 x 10(-8))。我们还发现rs2596542的风险等位基因与HCV诱发的HCC个体中较低的可溶性MICA蛋白水平相关(P = 1.38 x 10(-13))。
To identify the genetic susceptibility factor(s) for hepatitis C virus-induced hepatocellular carcinoma (HCV-induced HCC), we conducted a genome-wide association study using 432,703 autosomal SNPs in 721 individuals with HCV-induced HCC (cases) and 2,890 HCV-negative controls of Japanese origin. Eight SNPs that showed possible association (P < 1 x 10(-5)) in the genome-wide association study were further genotyped in 673 cases and 2,596 controls. We found a previously unidentified locus in the 5' flanking region of MICA on 6p21.33 (rs2596542, P-combined = 4.21 x 10(-13), odds ratio = 1.39) to be strongly associated with HCV-induced HCC. Subsequent analyses using individuals with chronic hepatitis C (CHC) indicated that this SNP is not associated with CHC susceptibility (P = 0.61) but is significantly associated with progression from CHC to HCC (P = 3.13 x 10(-8)). We also found that the risk allele of rs2596542 was associated with lower soluble MICA protein levels in individuals with HCV-induced HCC (P = 1.38 x 10(-13)).